ABSTRACT Prompted by the finding in rodents that local sleep, as assessed through OFF period detection in multiunit recordings, is accompanied in the local EEG by slow activity, we will establish if local sleep also occurs in humans, and if it is related to intense learning involving circumscribed regions of cortex. Preliminary results presented in this Project indicate that in humans, as in rodents, cortical areas heavily involved in learning a task show a progressive increase in the occurrence of slow activity (2-9Hz) detected with hdEEG. To better characterize these effects, we will use an implicit rotation learning task that relies on a sensorimotor-parietal network, and a declarative visual sequence learning task with a prominent working memory component that relies on frontal and occipito-temporal cortex. In Aim 1, we will establish if intense training in each task results in the occurrence of local, regionally specific, slow activity in the spontaneous EEG. In Aim 2, we will test if intense training leads to specific impairment in performance tests involving the same brain regions, and if errors are associated, on a trial-by-trial basis, with local EEG slow activity in specific areas and at specific times, depending on the nature of the task and the stage of the test. In Aim 3, we will test whether local EEG slow activity in wake is due to intense synaptic plasticity (tiredness), like sleep, or instead is merely fatigue due to intense activity. We will also establish if sleep is necessary, rather than just rest, is necessary and sufficient to counteract local EEG slowing and tiredness. If successful, these studies, complemented by those of Project I (flies) and II (mice), will open new ways to investigating the occurrence, consequences and opportunities for the prevention of local sleep in neurological and psychiatric disorders.